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Biomarkers of Autoimmune Chronic Spontaneous Urticaria

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Abstract

Purposeof Review

Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers.

Recent Findings

Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy).

Summary

Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic.

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Abbreviations

ASST:

Autologous serum skin test

APST:

Autologous plasma skin test

BAT:

Basophil activation test, using donor basophils and the patient’s serum

BHRA:

Basophil histamine release assay

CBC:

Complete blood count

CindU:

Chronic inducible urticaria

CSU:

Spontaneous urticaria

DPU:

Delayed pressure urticaria

ESR:

Erythrocyte sedimentation rate

FcεRI:

High affinity receptor of IgE

Ig:

Immunoglobulin

MRGPRX2:

Mas-related G protein-coupled receptor X2

SHIP:

Src homology 2 (SH2)-containing inositol phosphatases

SYK:

Spleen tyrosine kinase pathway

TG:

Thyroglobulin

TPO:

Thyroid peroxidase

UV:

Urticarial vasculitis

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Authors and Affiliations

  1. Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Puente de Piedra 150, T2-602 Colonia Toriello-Guerra, Delegación Tlalpan, 14050, Mexico City, Mexico

    Désirée Larenas-Linnemann

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Désirée Larenas-Linnemann did the literature search, made the figure and tables (all original), and wrote the article.

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Correspondence to Désirée Larenas-Linnemann.

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Conflict of Interest

Dr. Larenas Linnemann reports personal fees from ALK, Astrazeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GSK national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot, grants from Abbvie, Bayer, Lilly, Sanofi, Astrazeneca, Pfizer, Novartis, Circassia, UCB, GSK., outside the submitted work. She is a coordinator of the immunotherapy committee of CMICA and general coordinator of ten national guidelines in the field of allergy, asthma, and immunotherapy.

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Larenas-Linnemann, D. Biomarkers of Autoimmune Chronic Spontaneous Urticaria. Curr Allergy Asthma Rep 23, 655–664 (2023). https://doi.org/10.1007/s11882-023-01117-7

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